Summary Objective To identify the independent relation of synovitis with incident radiographic knee osteoarthritis (OA) after adjusting for other structural factors known to cause synovitis. Design ...We examined MRIs from knees that developed incident radiographic OA from the Multicenter Osteoarthritis Study (MOST) and compared these case knees with controls that did not develop OA. We examined baseline MRIs for knees developing OA at any time up to 84 months follow-up. We scored lesions in cartilage, meniscus, bone marrow and synovitis. Synovitis scores were summed (0–9) across three regions, suprapatellar, infrapatellar and intercondylar region, each of which was scored 0–3. After bivariate analyses examining each factor's association with incidence, we carried out multivariable regression analyses adjusting for age, sex, BMI, alignment and cartilage and meniscal damage. Results We studied 239 case and 731 control knees. In bivariate analyses, cartilage lesions, meniscal damage, synovitis and bone marrow lesions were all risk factors for OA. After multivariable analyses, synovitis was associated with incident OA. A higher synovitis score increased the risk of incident OA (adjusted OR per unit increase 1.1; (95% CI 1.0, 1.2, P = .02)), but increased risk was associated only with synovitis scores of ≥3 (adjusted OR 1.6; 95% CI 1.2, 2.1, P = .003). Conclusions Synovitis, especially when there is a substantial volume within the knee, is an independent cause of OA.
Summary Objective Quadriceps weakness has been reported with incident but not progressive knee osteoarthritis (OA) in longitudinal studies. This study examined the relationship between quadriceps ...strength and worsening of knee joint space narrowing (JSN) over 30 months. Methods Longitudinal, observational study of adults aged 50–79 years with OARSI JSN score <3 at baseline. Baseline measures included bilateral weight-bearing fixed flexion radiographs, isokinetic concentric quadriceps and hamstring strength, height and weight, and physical activity. Hamstring:quadriceps (H:Q) strength ratios also were evaluated. Worsening was defined as an increase in JSN score in the tibiofemoral and/or patellofemoral compartments on 30-month radiographs or total knee replacement. Knee-based analyses used generalized estimating equations, stratified by sex, to assess relationships between strength and knee JSN while controlling for covariance between knees within subjects as well as age, body mass index (BMI), history of knee injury and/or surgery, physical activity level and alignment. Results 3856 knees (2254 females and 1602 males) with JSN score <3 at baseline and no missing follow-up data were included. Mean ± SD age was 62.2 ± 7.7 in women and 61.6 ± 8.1 in men. Women in the lowest tertile of quadriceps strength had an increased risk of whole knee JSN (OR = 1.66, 95% CI = 1.26, 2.19) and tibiofemoral JSN (OR = 1.69, 95% CI = 1.26, 2.28). However, no associations were found between strength and JSN in men or H:Q < 0.6 and JSN in men or women. Conclusions In women but not in men, quadriceps weakness was associated with increased risk for tibiofemoral and whole knee JSN.
Objective To examine the relation of radiographic features of osteoarthritis to knee pain in people with knees discordant for knee pain in two cohorts.Design Within person, knee matched, case-control ...study.Setting and participants Participants in the Multicenter Osteoarthritis (MOST) and Framingham Osteoarthritis studies who had knee radiographs and assessments of knee pain.Main outcome measures Association of each pain measure (frequency, consistency, and severity) with radiographic osteoarthritis, as assessed by Kellgren and Lawrence grade (0-4) and osteophyte and joint space narrowing grades (0-3) among matched sets of two knees within individual participants whose knees were discordant for pain status.Results 696 people from MOST and 336 people from Framingham were included. Kellgren and Lawrence grades were strongly associated with frequent knee pain—for example, for Kellgren and Lawrence grade 4 v grade 0 the odds ratio for pain was 151 (95% confidence interval 43 to 526) in MOST and 73 (16 to 331) in Framingham (both P<0.001 for trend). Similar results were also seen for the relation of Kellgren and Lawrence scores to consistency and severity of knee pain. Joint space narrowing was more strongly associated with each pain measure than were osteophytes.Conclusions Using a method that minimises between person confounding, this study found that radiographic osteoarthritis and individual radiographic features of osteoarthritis were strongly associated with knee pain.
Summary Objective To determine whether women experience greater knee pain severity than men at equivalent levels of radiographic knee osteoarthritis (OA). Design and methods A cross-sectional ...analysis of 2712 individuals (60% women) without knee replacement or a recent steroid injection. Sex differences in pain severity at each Kellgren–Lawrence (KL) grade were assessed by knee using visual analog scale (VAS) scale and Western Ontario and McMaster Universities Arthritis Index (WOMAC) with and without adjustment for age, analgesic use, Body mass index (BMI), clinic site, comorbid conditions, depression score, education, race, and widespread pain (WSP) using generalized estimating equations. Effect sizes (Cohen's d ) were also calculated. Analyses were repeated in those with and without patellofemoral OA (PFOA). Results Women reported higher VAS pain at all KL grades in unadjusted analyses ( d = 0.21–0.31, P < 0.0001–0.0038) and in analyses adjusted for all covariates except WSP ( d = 0.16–0.22, P < 0.0001–0.0472). Pain severity differences further decreased with adjustment for WSP ( d = 0.10–0.18) and were significant for KL grade ≤2 ( P = 0.0015) and 2 ( P = 0.0200). Presence compared with absence of WSP was associated with significantly greater knee pain at all KL grades ( d = 0.32–0.52, P < 0.0001–0.0008). In knees with PFOA, VAS pain severity sex differences were greater at each KL grade ( d = 0.45–0.62, P = 0.0006–0.0030) and remained significant for all KL grades in adjusted analyses ( d = 0.31–0.57, P = 0.0013–0.0361). Results using WOMAC were similar. Conclusions Women reported greater knee pain than men regardless of KL grade, though effect sizes were generally small. These differences increased in the presence of PFOA. The strong contribution of WSP to sex differences in knee pain suggests that central sensitivity plays a role in these differences.
Summary Objective To determine the association of varus thrust during walking to incident and worsening medial tibiofemoral cartilage damage and bone marrow lesions (BMLs) over two years in older ...adults with or at risk for OA. Method Subjects from the Multicenter Osteoarthritis Study were studied. Varus thrust was visually assessed from high-speed videos of forward walking trials. Baseline and two-year MRIs were acquired from one knee per subject and read for cartilage loss and BMLs. Logistic regression with generalized estimating equations was used to estimate the odds of incident and worsening cartilage loss and BMLs, adjusting for age, sex, race, body mass index, and clinic site. The analysis was repeated stratified by varus, neutral, and valgus alignment. Results 1007 participants contributed one knee each. Varus thrust was observed in 29.9% of knees. Knees with thrust had 2.17 95% CI: 1.51, 3.11 times the odds of incident medial BML, 2.51 1.85, 3.40 times the odds of worsening medial BML, and 1.85 1.35, 2.55 times the odds of worsening medial cartilage loss. When stratified by alignment, varus knees also had significantly increased odds of these outcomes. Conclusion Varus thrust observed during walking is associated with increased odds of incident and worsening medial BMLs and worsening medial cartilage loss. Increased odds of these outcomes persist in varus-aligned knees.
There is an interest in identifying a metabolic OA phenotype. We therefore assessed the relation of diabetes and cardiovascular disease to prevalent and incident radiographic (ROA) and symptomatic ...knee osteoarthritis (SxOA).
In two large cohort studies of individuals with or at risk for knee OA, the Multicenter Osteoarthritis Study (MOST) and Osteoarthritis Initiative (OAI), participants self-reported diabetes and cardiovascular disease (CVD) at baseline. We assessed the relation of baseline diabetes and CVD (exposures) to ROA and SxOA cross-sectionally and after 60 (MOST) or 48 (OAI) months of follow-up using logistic regression with GEE to account for 2 knees within an individual, adjusting for potential confounders.
In MOST, 6,020 knees of 3,021 participants (60.1% female, mean ± SD age 62.5 ± 8.1, mean BMI 30.7 ± 6.0, 83.3% Caucasian) were included in the analyses. In OAI, 8,645 knees of 4,339 participants (58.2% female, mean ± SD age 61.1 ± 9.2, mean BMI 28.6 ± 4.8, 80.3% Caucasian) were included. We found no significant associations between prevalent diabetes or CVD and prevalent or incident ROA or SxOA. Effect estimates for prevalent ROA and SxOA ranged from 0.80 (95% CI 0.63–1.03) to 1.17 (0.91–1.51). Effect estimates for incident ROA ranged from 0.80 (0.58–1.11) to 0.88 (0.60–1.29) in MOST and from 0.75 (0.50–1.14) to 1.19 (0.81–1.74) in OAI, and for incident SxOA from 0.93 (0.65–1.31) to 1.22 (0.89–1.67) in MOST and from 0.82 (0.59–1.16) to 1.19 (0.85–1.66) in OAI).
Diabetes and CVD were not associated with prevalent or incident knee OA.
To determine the relationship of meniscal damage to magnetic resonance imaging (MRI) features of compartment-specific patellofemoral joint (PFJ) osteoarthritis (OA) at baseline and 2 years later.
...Individuals from a prospective cohort of individuals aged 50–79 with or at risk of knee OA were included. At the 60-month and 84-month study visit, Whole-Organ MRI Score (WORMS) was used to assess meniscal tears and extrusions as well as cartilage damage and bone marrow lesions (BMLs) in the medial and lateral patella and trochlea. Worsening of structural features was defined as any increase in WORMS score from 60 to 84 months. Logistic regression was used to determine the cross-sectional and longitudinal relation of meniscus damage to features of compartment-specific PFJ OA.
Relative to knees without lateral meniscal pathology at baseline, those with grades 3–4 lateral meniscal tear and extrusion had greater risk of worsening of cartilage damage in the lateral PFJ 2 years later (Risk ratio: 1.7 95% CI: 1.1–2.7) and (1.7 1.2–2.5), respectively. Relative to those without medial meniscal pathology at baseline, those with grades 1–2 (0.6 0.4–0.9) and 3–4 (0.7 0.5–1.0) medial meniscal tears had lower risk of worsening of BMLs in the medial PFJ 2 years later.
Meniscal tear and extrusion are associated with increased risk of medial and lateral PFJ OA and more severe meniscal pathology is associated with worsening of PFJ OA 2 years later. Lateral meniscal pathology appears to be more detrimental to the lateral PFJ.
Summary Objectives To provide a comprehensive simultaneous relation of various semiquantitative knee OA MRI features as well as the presence of baseline radiographic osteoarthritis (OA) to ...quantitative longitudinal cartilage loss. Methods We studied Multicenter OA Study (MOST) participants from a longitudinal observational study that included quantitative MRI measurement of cartilage thickness. These subjects also had Whole Organ MRI Score (WORMS) scoring of cartilage damage, bone marrow lesions (BMLs), meniscal pathology, and synovitis, as well as baseline radiographic evaluation for Kellgren and Lawrence (KL) grading. Knee compartments were classified as progressors when exceeding thresholds of measurement variability in normal knees. All potential risk factors of cartilage loss were dichotomized into “present” (score ≥2 for cartilage, ≥1 for others) or “absent”. Differences in baseline scores of ipsi-compartmental risk factors were compared between progressor and non-progressor knees by multivariable logistic regression, adjusting for age, sex, body mass index, alignment axis (degrees) and baseline KL grade. Odds ratios (OR) and 95% CIs were calculated for medial femorotibial compartment (MFTC) and lateral femorotibial compartment (LFTC) cartilage loss. Cartilage loss across both compartments was studied using Generalized Estimating Equations. Results 196 knees of 196 participants were included (age 59.8 ± 6.3 years mean ± SD, BMI 29.5 ± 4.6, 62% women). For combined analyses of MFTC and LFTC, baseline factors related to cartilage loss were radiographic OA (KL grade ≥2: aOR 4.8 2.4–9.5, cartilage damage (aOR 2.3 1.2–4.4)), meniscal damage (aOR 3.9 2.1–7.4) and extrusion (aOR 2.9 1.6–5.3), all in the ipsilateral compartment, but not BMLs or synovitis. Conclusion Baseline radiographic OA and semiquantitatively (SQ) assessed MRI-detected cartilage damage, meniscal damage and extrusion, but not BMLs or synovitis is related to quantitatively measured ipsi-compartmental cartilage thinning over 30 months.
Summary Objective To determine whether quadriceps weakness is associated with elevated risk of worsening knee pain over 5 years. Methods The Multicenter Osteoarthritis Study (MOST) is a longitudinal ...study of 50–79-year-old adults with knee osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was baseline isokinetic quadriceps strength. Covariates included baseline body mass index (BMI), physical activity level, and history of knee surgery. The outcome was worsening pain reported on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between baseline and 5-year follow-up. Analyses were knee-based and used generalized estimating equations, stratified by sex to assess whether the lowest compared with the highest tertile of baseline quadriceps strength was associated with an increased risk of worsening knee pain at 5-year follow-up, controlling for age, BMI, history of knee surgery, and physical activity level as well as correlation between knees within participants. Results Analyses of worsening knee pain included 4,648 knees from 2,404 participants (61% female). Men with lower quadriceps strength did not have a higher risk of worsening knee pain (RR {95% CI} = 1.01 {0.78–1.32}, P = 0.9183). However, women in the lowest compared with the highest strength tertile had a 28% increased risk of worsening knee pain (RR {95% CI} = 1.28 {1.08–1.52}, P = 0.0052). Conclusion Quadriceps weakness was associated with an increased risk of worsening of knee pain over 5 years in women, but not in men.
Summary Objective To determine what MRI-detectable osteoarthritis features that are not visualized on radiography demonstrate progression longitudinally in Kellgren and Lawrence (KL) grade 4 knees. ...Methods We studied subjects from the Multicenter Osteoarthritis Study who had KL grade 4 knees at baseline and had baseline and 30-month MRI. Cartilage damage, bone marrow lesions (BMLs), meniscal damage, synovitis (signal changes in Hoffa fat pad), and effusion (fluid equivalent signal in the joint cavity) were semiquantitatively scored using the Whole Organ MRI Score (WORMS) system in five subregions of the medial and lateral tibiofemoral (TF) compartments. Analysis was performed for the compartment showing bone-on-bone appearance (“index”) on radiograph and also for the other TF compartment of the same knee. Synovitis and effusion were assessed for the whole knee. Changes in scores at follow-up were noted for each feature. For cartilage and BML, within-grade changes were also recorded. Results 140 subjects (164 knees) were included (50% women, mean age 66.0 ± 8.6 years, mean BMI 30.4 ± 5.1 kg/m2 ). Longitudinally, 51 index compartments (34%) showed an increase in the sum of cartilage scores from all subregions. In the other compartment, 25% showed an increase in the sum score for cartilage damage. For BMLs in the index compartment, 50 knees (33%) showed an increase in maximum score and 32 (21%) showed a decrease. Meniscal status mostly remained stable. Effusion worsened in 36 knees (25%) and improved in 13 knees (9%). Synovitis worsened in 14 knees (10%) and improved in six knees (4%). Conclusion In KL grade 4 knees, MRI-detected cartilage loss and fluctuation of BMLs, effusion, and synovitis occurred frequently over a 30-month period.
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